COMPARISON OF THE EFFECT OF THE MACROLIDE ANTIBIOTICS ERYTHROMYCIN, CLARITHROMYCIN AND AZITHROMYCIN ON TERFENADINE STEADY-STATE PHARMACOKINETICS AND ELECTROCARDIOGRAPHIC PARAMETERS
COMPARISON OF THE EFFECT OF THE MACROLIDE ANTIBIOTICS ERYTHROMYCIN, CLARITHROMYCIN AND AZITHROMYCIN ON TERFENADINE STEADY-STATE PHARMACOKINETICS AND ELECTROCARDIOGRAPHIC PARAMETERS
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DOI：
10.1007/bf03258467
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发表时间：
1994-03-01
期刊：
影响因子：
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通讯作者：
CANTILENA, LR
中科院分区：
文献类型：
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作者：
HONIG, PK;WORTHAM, DC;CANTILENA, LR
特非那定是一种非镇静的组胺H-1拮抗剂，与酮康唑一起给药时，会导致母体特非那定在易感个体体内蓄积，并改变心脏复极。这项前瞻性队列研究旨在评估大环内酯类药物对特非那定药代动力学和心电图参数的影响，评估了18名服用特非那定稳定状态的健康男性和女性志愿者。相同数量的患者(6人)随机接受红霉素、克拉霉素或阿奇霉素的推荐剂量治疗，同时继续服用特非那定。同时考察了大环内酯类单药治疗对心电图的影响。对加入大环内酯类药物前后的特非那定进行了药代动力学分析，并在基线和采血日给药前采集心电图。红霉素和克拉霉素显著影响特非那定的药代动力学。接受红霉素治疗的6名志愿者中的3名和接受克拉霉素治疗的6名志愿者中的4名显示出与心脏复极改变相关的可量化的未代谢特非那定的积聚。阿奇霉素对特非那定的药代动力学和心脏药效学均无影响。
Terfenadine is a nonsedating histamine H-1-antagonist that, when given with ketoconazole, results in accumulation of parent terfenadine and altered cardiac repolarisation in susceptible individuals. This prospective cohort study, designed to assess macrolide effects on terfenadine pharmacokinetics and electrocardiogram (ECG) parameters, evaluated 18 healthy male and female volunteers who received terfenadine to steady-state. Equal numbers (6) were randomised to receive either erythromycin, clarithromycin or azithromycin at recommended doses while continuing terfenadine. Macrolide monotherapy effects on the ECG were also investigated. Pharmacokinetic profiles for terfenadine were performed before and after the addition of macrolide therapy, and ECGs were obtained at baseline and predose on days of blood sampling.Erythromycin and clarithromycin significantly affected the pharmacokinetics of terfenadine. Three of 6 volunteers receiving erythromycin and 4 of 6 receiving clarithromycin demonstrated accumulation of quantifiable unmetabolised terfenadine that was associated with altered cardiac repolarisation. Azithromycin had no effect on terfenadine pharmacokinetics or cardiac pharmacodynamics.